Crosstalk Between Mucosal Inflammation and Bone Metabolism in Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is a multifactorial and highly heterogeneous upper airway disease that affects approximately 12% of the general population. There is increasing evidence supporting the impact of osteitis on the pathophysiology of CRS. Osteitis is frequently observed in patients with CRS, and is associated with severe sinonasal inflammation and recalcitrant cases. The overlying inflammatory sinonasal mucosa plays a critical role in the initiation of osteitis; however, the underlying molecular mechanisms and functional significance remain unclear. Increasingly many studies have suggested that immune cells play a crucial role in the bone remodeling process in CRS. The purpose of this review is to summarize the current state of knowledge regarding the specific role of sinonasal inflammation in bone remodeling in CRS patients.

Evaluation of Neo-Osteogenesis in Eosinophilic Chronic Rhinosinusitis Using a Nasal Polyp Murine Model

PURPOSE: Osteitis refers to the development of new bone formation and remodeling of bone in chronic rhinosinusitis (CRS) patients; it is typically associated with eosinophilia, nasal polyps (NPs), and recalcitrant CRS. However, the roles of ossification in CRS with or without NPs remain unclear due to the lack of appropriate animal models. Thus, it is necessary to have a suitable animal model for greater advances in the understanding of CRS pathogenesis.METHODS: BALB/c mice were administered ovalbumin (OVA) and staphylococcal enterotoxin B (SEB). The numbers of osteoclasts and osteoblasts and bony changes were assessed. Micro computed tomography (micro-CT) scans were conducted to measure bone thickness. Immunofluorescence, immunohistochemistry, and quantitative polymerase chain reaction were performed to evaluate runt-related transcription factor 2 (RUNX2), osteonectin, interleukin (IL)-13, and RUNX2 downstream gene expression. Gene set enrichment analysis was performed in mucosal tissues from control and CRS patients. The effect of resveratrol was evaluated in terms of osteogenesis in a murine eosinophilic CRS NP model.RESULTS: The histopathologic changes showed markedly thickened bones with significant increase in osteoblast numbers in OVA/SEB-treated mice compared to the phosphate-buffered saline-treated mice. The structural changes in bone on micro-CT were consistent with the histopathological features. The expression of RUNX2 and IL-13 was increased by the administration of OVA/SEB and showed a positive correlation. RUNX2 expression mainly co-localized with osteoblasts. Bioinformatic analysis using human CRS transcriptome revealed that IL-13-induced bony changes via RUNX2. Treatment with resveratrol, a candidate drug against osteitis, diminished the expression of IL-13 and RUNX2, and the number of osteoblasts in OVA/SEB-treated mice.CONCLUSIONS: In the present study, we found the histopathological and radiographic evidence of osteogenesis using a previously established murine eosinophilic CRS NP model. This animal model could provide new insights into the pathophysiology of neo-osteogenesis and provide a basis for developing new therapeutics.

Impact of the Long-Lived Plasma Cells in Patients With Chronic Rhinosinusitis With Nasal Polyps

No abstract available.

Immune Cell Responses and Mucosal Barrier Disruptions in Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is one of the most common presentations of upper airway illness and severely affects patient quality of life. Its frequency is not surprising given levels of environmental exposure to microbes, pollutants, and allergens. Inflammatory cells, inflammatory cytokine and chemokine production, and airway remodeling have been detected in the sinonasal mucosae of CRS patients, although the precise pathophysiological mechanisms causing such persistent inflammation remain unclear. Given its high prevalence and considerable associated morbidity, continued research into CRS is necessary to increase our understanding of factors likely to contribute to its pathogenesis, and facilitate the development of novel therapeutic strategies to improve treatment. The purpose of this review is to summarize the current state of knowledge regarding immune cell responses and epithelial alterations in CRS.

Serial Analysis of Tracheal Restenosis After 3D-Printed Scaffold Implantation: Recruited Inflammatory Cells and Associated Tissue Changes

Tracheal restenosis is a major obstacle to successful tracheal replacement, and remains the greatest challenge in tracheal regeneration. However, there have been no detailed investigations of restenosis. The present study was performed to analyze the serial changes in recruited inflammatory cells and associated histological changes after tracheal scaffold implantation. Asymmetrically porous scaffolds, which successfully prevented tracheal stenosis in a partial trachea defect model, designed with a tubular shape by electrospinning and reinforced by 3D-printing to reconstruct 2-cm circumferential tracheal defect. Serial rigid bronchoscopy, micro-computed tomography, and histology [H&E, Masson's Trichrome, IHC against a-smooth muscle actin (α-SMA)] were performed 1, 4, and 8 weeks after transplantation. Progressive stenosis developed especially at the site of anastomosis. Neutrophils were the main inflammatory cells recruited in the early stage, while macrophage infiltration increased with time. Recruitment of fibroblasts peaked at 4 weeks and deposition of a-SMA increased from 4 weeks and was maintained through 8 weeks. During the first 8 weeks post-transplantation, neutrophils and macrophages played significant roles in restenosis of the trachea. Antagonists to these would be ideal targets to reduce restenosis and thus play a pivotal role in successful tracheal regeneration.

Immunohistochemical Study on beta1- and beta2-Adrenergic Receptors in Rat Vestibular Nuclei / 대한평형의학회지

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the localizations of beta1- and beta2-adrenergic receptors (ARs) in rat vestibular nuclei by immunohistochemical staining procedure. MATERIALS AND METHODS: Twelve male Sprague-Dawley rats were used in this study. Primary antibodies for the beta1- and beta2-ARs were used. The sections were treated with a biotinylated goat anti-rabbit antibody. The sections were then incubated in avidin-biotin-peroxidase reagent and processed with immunoperoxidase using 3.3'-diaminobenzidine tetrahydrochloride. RESULTS: beta1-AR and beta2-AR immunopositive neurons were found to be distributed throughout the four major vestibular nuclei. Both receptors were primarily detected in neuronal somata and their proximal dendrites. beta1-AR and beta2-AR were moderately expressed in the superior vestibular nucleus, lateral vestibular nucleus, medial vestibular nucleus, and spinal vestibular nucleus. CONCLUSION: The present study demonstrates, for the first time, that beta1-AR and beta2-AR receptors are localized in rat vestibular nuclei. Furthermore, this study may provide additional speculation into the role of ARs during vestibular signal processing. Further studies are needed to clarify the roles played by beta1-ARs and beta2-ARs through physiologic and functional studies.

Roles of Periostin in Symptom Manifestation and Airway Remodeling in a Murine Model of Allergic Rhinitis

PURPOSE: Periostin was originally identified as a secreted factor during screening of a mouse osteoblastic library. In a recent study, periostin was found to directly regulate eosinophil accumulation in allergic mucosal inflammation. Chronic eosinophilic inflammation is related to the development of remodeling. The present study examined the expression of periostin and evaluated its role in the inflammatory process and remodeling associated with allergic rhinitis. METHODS: A murine model of allergic rhinitis was established in periostin knockout mice. We analyzed the expression of periostin, manifestation of nasal symptoms, eosinophilic inflammation, and subepithelial fibrosis as well as the expression of MMP-2, TIMP-1, and type 1 collagen in nasal tissue. RESULTS: Periostin was mainly distributed in the subepithelial tissue of the nasal mucosa. The subepithelial tissue was thinner in the knockout group than in the control group. No differences in the expression of MMP-2 or TIMP-1 were found in the knockout group. However, after a month of allergen challenge, type I collagen in the nasal tissue was lower in the knockout group than in the control group. The number of eosinophils and the symptom score were also lower in the knockout group. CONCLUSIONS: Periostin is expressed in nasal tissues of murine models of allergic rhinitis. Periostin deficiency may affect the remodeling of nasal tissue with reduced subepithelial fibrosis, and lead to less eosinophilic inflammation.

Quantitative Analysis of Myosin Heavy Chain Expression Change in Laryngeal Muscle after Irradiation in Rats

PURPOSE: Radiotherapy for head and neck cancer does not impair the voice quality as much as laser treatment or surgery, but it can induce muscle wasting and fibrosis and symptoms of dry mouth. We investigated the effect of irradiation on the myosin heavy chain (MyHC) expression in laryngeal muscles. MATERIALS AND METHODS: Rats were irradiated with one dose of 10, 15, 20, 25, 30, or 35 Gy and other rats were irradiated with 20 Gy. The thyroarytenoid (TA), posterior cricoarytenoid (PCA), and cricothyroid (CT) muscles were subjected to reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Two weeks after irradiation with 10, 15, or 20 Gy, all the MyHC type expressions had decreased in a dose-dependent manner in the TA, PCA, and CT muscles, and especially the expression of MyHC IIa decreased much more than the expressions of the other MyHC isoforms in all muscles. In the 20 Gy-irradiated rats, almost all the MyHC isoform expressions declined over 12 weeks in the TA, PCA, and CT muscles, except for the MyHC I expression in the PCA and CT muscle. The MyHC IIa expression was markedly decreased in all the muscles. CONCLUSION: The laryngeal muscles responded differently to radiation, but they showed a time-dependent and long-lasting decrease in the expressions of all the MyHC isoforms in the TA, PCA, and CT muscles. In particular, the expression of the MyHC IIa isoform in all the muscles may be more sensitive to irradiation than the expressions of the other MyHC isoforms.

A Rat Model of Acute Rhinosinusitis Induced by Alpha-Toxin of Staphylococcus Aureus

BACKGROUND AND OBJECTIVES: Staphylococcus Aureus (S. Aureus) is one of the most common and predominant form of bacteria in the nasal airway that roduces toxin. Alpha toxin from S. Aureus, also known as alpha-hemolysin, causes damage to the membrane in many types of cells. The purpose of this study is to develop a rat model of rhinosinusitis induced by the intra-nasally applied alpha-toxin of S. Aureus. MATERIAL AND METHODS: Forty micro-liters of 100 microgram/ml of alpha-toxin was applied intra-nasally to 4-6 weeks-old Sprague-Dawley rats and the same amount of vehicle was applied to control rats. At days 1, 5 and 14 the rats were sacrificed and their nasal cavity prepared for histological investigation. RESULTS: Inflammatory cell clusters were observed in the alpha-toxin applied rats. The number of sinus air spaces occupied by inflammatory cell clusters increased significantly at days 1 and 5 compared with the control rats. Comparisons across the time interval demonstrated statistically significant changes, showing a peak at day 1 among alpha-toxin applied rats. CONCLUSION: Intra-nasally applied alpha-toxin induces acute rhinosinusitis in the rats. The histological evidence of rhinosinusitis revealed the appearance of inflammatory cell clusters in the sinonasal air spaces. These findings indicate that this rat model of alpha-toxin induced rhinosinusitis may be applied for better understanding of the role of bacterial toxin in the pathogenesis of rhinosinusitis.